Technical Field
Agents and compositions thereof are described herein that are E-selectin antagonists and may be used as therapeutics. Methods are described for mobilizing cells from the bone marrow using the E-selectin antagonists described herein.
Description of the Related Art
Autologous hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach for various malignant hematologic and lymphoid diseases. Hematopoietic stem cells (HSCs) may be collected from the blood or the bone marrow and used for repopulating hematopoiesis. Recent studies demonstrate clinical advantages of re-infusing autologous mobilized peripheral blood stem cells compared with bone marrow HSCs (see, e.g., Lemoli et al., Haematologica 93:321-324 (2008); Gratwohl et al., Blood 100:2374-86 (2002)). The cytokine, granulocyte colony-stimulating factor (G-CSF), has been the agent predominantly used in the clinic for mobilization of HSCs. More recently, a chemokine (C-X-C motif) receptor 4 (CXCR4) antagonist, AMD3100 (also called plerixafor) has been administered alone or with G-CSF for this purpose.
Not all patients treated with G-CSF have successful mobilization of peripheral blood stem cells: as high as 25% of patients with lymphomas, multiple myeloma, or acute leukemia, and in 10-20% of normal volunteers, all of whom require extended aphereses (see, e.g., Pelus, Curr. Opin. Hematol. 15:285-92 (2008) and references cited therein). Studies are ongoing to identify additional agents to use alone or in combination with G-CSF to reduce the multidosing requirement and to improve long term quality of life.
Therefore, a need exists in the art to identify highly effective, non-toxic, and less expensive therapeutics useful for mobilizing peripheral blood stem cells.